Several types of cancer can affect the prostate gland, including adenocarcinoma, sarcoma, squamous cell carcinoma, and ductal transitional carcinoma. Adenocarcinoma is the most common of these and is one of the most common malignancies in men over 50 years old. In the United States, over 200,000 men become diagnosed with this type of cancer every year.
Most cancers of the prostate gland have androgen receptors. They depend on testosterone and other androgens for their growth. Hormone ablative therapy—therapy which chemically interferes with androgens or the organs that produce it—is therefore standard in the treatment of prostate cancer. Such therapy can prolong survival of men with prostate cancer from 3 to 5 years or more.
Chemical hormone ablative therapy includes the administration of drugs that block the hormonal pathways that lead to androgen synthesis. In the male, the hypothalamus secretes gonadotropin releasing hormone (“GnRH”), which stimulates the pituitary gland to secrete luteinizing hormone (“LH”); LH, in turn, stimulates the testes to produce testosterone. Synthetic analogs of GnRH and LH are therefore administered to reduce levels of androgens circulating within the body. These analogs compete with their natural counterparts for binding to GnrH receptors, thereby down-regulating the receptors and interrupting the testosterone production cycle. Estrogen also blocks androgen production, but can compromise cardiovascular health and so is rarely used. Antiandrogen drugs, such as flutamide, bicalutamide, or nilutamide, are also available. These bind to androgen receptors on prostate cancer cells, preventing their activation, and thereby limiting the action of natural androgens.
Surgical hormonal ablative therapy comprises surgical removal of one or both testes (orchiectomy), the testosterone-producing organ in the male. One may increase the effectiveness of this treatment still further by combining it with anti-androgens.
Androgen-independent prostate cancer (also called hormone refractory prostate cancer) does not depend on androgens for its growth; as a result, hormone ablative therapy has little effect on it. Even therapies that are highly effective at treating androgen-dependent cancers have been shown to be ineffective when applied to patients with androgen-independent cancer.
Androgen-independent cancer is difficult to treat. One can decrease the size of prostate inflammation associated with the cancer, such as with corticosteroids and other anti-inflammatory agents, but such treatment has no effect on the cancer itself. For this reason, a basic medical text still teaches that “There is no standard therapy for hormone refractory prostate cancer.” M. H. Beers and R. Berkow, eds., Merck Manual of Diagnosis and Therapy, 1658 (1999). According to this text, cytotoxic and biologic agents “are being investigated,” but “their superiority to corticosteroids alone has not been proved.”
There is therefore a significant need in the art for a satisfactory treatment of androgen-independent prostate cancer. Such a treatment could have a dramatic impact on the health of older men, among whom prostate cancer is common.